Download Pathophysiology of Pain

Pathophysiology of Pain
Nociception
The detection of tissue damage by
specialized transducers connected to
A-delta and C-fibers
Pain
An unpleasant sensory and emotional
experience which we primarily associate
with tissue damage or describe in terms of
such damage, or both
Classification of Pain Nociception
• Proportionate to the stimulation of the
nociceptor
• When acute
– Physiologic pain
– Serves a protective function
– Normal pain
• Pathologic when chronic
Classification of Pain:
Neuropathic Pain
• Sustained by aberrant processes in
PNS or CNS
• Disproportionate to the stimulation of
nociceptor
• Serves no protective function
• Pathologic pain
Classification of Pain: Mixed Pain
• Nociceptive components
• Neuropathic components
• Examples
– Failed low-back-surgery syndrome
– Complex regional pain syndrome
Classification of Pain: Idiopathic Pain
• No underlying lesion found yet, despite
investigation
• Pain disproportionate to the degree of
clinically discernible tissue injury
Normal Central Pain
Mechanisms
Peripheral and Central Pathways for Pain
Ascending Tracts
Descending Tracts
Cortex
Thalamus
Midbrain
Pons
Medulla
Spinal Cord
Pain-Inhibitory and Pain-Facilitatory
Mechanisms Within the Dorsal Horn
0
A-BETA
A-DELTA
_ _
Neuronal circuitry
within the dorsal horn.
Primary afferent neuron
axons synapse onto
spinothalamic neurons
and onto inhibitory and
excitatory neurons.
+
+
STT
NEURON
++
TO BRAIN
C
Rating of First and Second Pain Intensity
Adapted with permission from Cooper BY, et al. Pain. 1986;24:103 and from Lee KH, et al. In: Fields HL, Dubner
R, Cervero F, eds. Proceedings of the Fourth World Congress on Pain. New York, NY: Raven Press; 1985:204.
Mechanisms of Pathologic Pain
Mechanisms of Pathologic Pain:
General Considerations
• Pain-processing mechanisms function
abnormally
– Examples: neuropathic pain syndromes
• Nociception is sustained by chronic injury
– Example: arthritis
Mechanisms of Pathophysiologic Pain:
Peripheral Processes
• Injured or diseased nerve(s)
• Growth of axonal sprouts
• Formation of ectopic foci
Mechanisms of Pathophysiologic Pain:
Central Sensitization Processes
• Repeated impulse activity in C nociceptive
•
neurons produces sensitization of STT neurons
over time
Sensitization of STT neurons leads to
– Increased spontaneous impulse activity
– Enhanced responses to impulses in nociceptive and
non-nociceptive primary afferents
• Causes hyperalgesia, allodynia, and
spontaneous pain
Temporal summation
of second pain
(second pain
summation is a result
of repeated input from
C-fiber).
Temporal summation of
responses of a dorsal
horn (STT) neuron to
repeated C-fiber
stimulation and the
effects of the NMDAreceptor antagonist
ketamine.
Reproduced with permission from Price DD, et al. In: Fields HL, Liebeskind JC, eds. Pharmacological Approaches to the
Treatment of Chronic Pain: New Concepts and Critical Issues. Seattle, Wash: IASP Press; 1994:66.
Mechanism of Central Sensitization Associated
With Tonic C Nociceptor Input
0
A-BETA
A-DELTA
C
Tonic activity in
C nociceptors
_ _
+
+
+
STT
++
NEURON
++
++
TO BRAIN
Enhanced postsynaptic
effects by NMDAreceptor sensitization
Intracellular
Mechanisms
of
Sensitization
Reproduced with permission from Mao J, et
al. Pain. 1995;61:361.
Loss of Inhibitory Interneuron Function
0
A-BETA
A-DELTA
Tonic activity in
C nociceptors
_ _
+
C
+
STT
NEURON
++
++
++
TO BRAIN
Enhanced postsynaptic
effects by NMDAreceptor sensitization
Brain-to-Spinal-Cord
Modulation of Pain
Pain Modulation Mechanisms
• Brain centers/pathways that descend to the
spinal cord and modulate pain
• “Tail-flick test”
• “Off-cells” inhibit transmission of painrelated information to the brain
• “On-cells” facilitate transmission of painrelated signals to the brain
Pathophysiology of Pain: Conclusion
• Neuronal plasticity
– Nociceptor, spinal cord, brain
• Pain-facilitatory and pathophysiologic
mechanisms
– Wind-up phenomenon
– Central sensitization
• Modulating mechanisms
– Ascending
– Descending